Safety and Efficacy of GBC/GBM Conditioning Regimen Followed By Autologous Stem Cell Transplantation in Lymphoid Malignancies

Objective: To investigate the safety and efficacy of high-dose infusional gemcitabine combined with busulfan and cyclophosphamide (GBC) or melphalan (GBM) followed by autologous stem-cell transplantation (ASCT) in lymphoid malignancies.

Methods: We retrospectively analyzed 73 and 21 patients of lymphoma, who received GBC and GBM conditioning regimen with ASCT respectively in our center from May 2017 to April 2020. Gemcitabine (600mg·m^-2·h^-1×3h) was given on day -7 and -3, busulfan (105mg/ m²) from day -7 to -5, followed by cyclophosphamide (50mg/kg) or melphelan (60mg/m²) from day -3 to -2. Autologous stem cells were reinfused on day 0. The side effects, hematopoiesis recovery time, 3-year progression free survival (PFS) and 3-year overall survival (OS) were observed.

Results: Ninety-four patients were enrolled in this study. Among them, 63 cases (67%) were in the first line treatment，including 55 cases in CR1 and 8 cases in PR1, while 31 cases (33%) were in or after second line treatment, including 23 cases in CR, 7 cases in PR and 1 case in SD. There were 32 cases of large B-cell lymphoma (LBCL), 14 cass of mantle cell lymphoma (MCL) and 8 cases of peripheral T cell lymphoma (PTCL) in the first line treatment group, while 12 cases of Hodgkin lymphoma (HL) and 10 cases of LBCL in the non-first line treatment group. A median number of 3.09 (range 0.71-21.33) ×10⁶/kg CD34 cells were infused. The grade 3 or 4 toxicities were neutropenia (100%), thrombocytopenia (100%), anemia (81%), oral mucositis (45%), hepatopathy (23%), nausea (14%), diarrhea (20%), vomiting (5%), hemorrhage (4%) and fever (1%). Bacterial infection was found in 9 cases (10%), and fungal infection in 2 cases (4%). The median time to neutrophil engraftment was 10 days (range, 8-28) and platelet engraftment was 11 days (range, 0-63). VOD and treatment-related death did not occur during the study. After a median follow-up of 21 months, the estimated 3-year PFS and OS rate of all patients was 84% and 92% respectively. The estimated 3-year PFS rates of patients in the first-line treatment group and the non-first line treatment group were 90% and 67%, respectively (P=.0134), while the estimated 3-year OS rates were 93% and 87%, respectively (P=.8235). The estimated 28-month PFS rates of first line treatment patients in the CR group and PR group were 90% and 88%, respectively (P=.7760), while the estimated 28-month OS rates were 94% and 88%, respectively (P=.4361). The estimated 3-year PFS rates of non-first line treatment patients in the CR group and PR group were 71% and 67%, respectively (P=.8748), while the estimated 3-year OS rates were 92% and 67%, respectively (P=.2014).

Conclusion: In this retrospective analysis, our results demonstrate that GBC/GBM conditioning regimens with ASCT are feasible with tolerable toxicity and improved outcomes in PR patients whether in first line or non-first line treatment, which appears be an alternative to the classical conditioning regimens for ASCT in lymphoid malignancies.